This is a revised application to establish a NIEHS Center in Environmental Health Sciences at the University of Pennsylvania. The Center will hold the title: "Center for Excellence in Environmental Toxicology (CEET)". It will be the single entity that coordinates, facilitates, synergizes and integrates all environmentally related health research and outreach at the University. The CEET has identified 50 faculty members in 16 Departments from 5 Schools as Center members. These members are dedicated to the CEET mission, which is: to improve the health of the public living in urban environments with an aging industrial infrastructure, through basic, translational and clinical research, and outreach. The investigators will relate environmental exposures, to molecular/cellular effects, to health outcomes, with the vision that diseases with environmental etiology can be largely eliminated by effective prevention or intervention strategies and/or changes in environmental policy. The mission will be accomplished via four integrated Research Cores, three Facility Cores, and a vibrant Community Outreach and Education Program (COEP). The Research Cores are led by investigators with international reputations. These Cores are in Oxidative Stress and Oxidative Stress Injury (co-Directors: Drs. Blair and Ischiropoulos), Endocrine and Reproduction Disruption (co-Directors: Drs. Strauss and Manson), Lung and Airway Disease (co-Directors: Drs. Panettieri and Albelda), and Genes and the Environment (co-Directors: Drs. Rebbeck and Whitehead). These Cores address environmental health issues important to our urban region. Adverse reproductive and pregnancy outcomes, developmental disorders, and diseases of the lung and airway are common, and are addressed in the organ-based Cores. The Cores in Oxidative Stress and Genes in the Environment will elucidate key mechanisms by which environmental exposures can lead to toxicity in these and other organ systems leading to an integrated Center structure. The Facility Cores will be in Toxicogenomics, Toxicoproteomics and Biomarkers, and will provide investigators with services that would otherwise be unattainable and will propel investigators into the new era of predictive toxicology. The COEP will disseminate the research findings and utilize the expertise of CEET investigators: to enhance K-16 education in environmental health; to conduct community outreach in four environmentally challenged Southeastern Pennsylvania communities, and to enrich the education of health care professionals. The COEP has forged relationships with community partners for outreach. The COEP goal will be to reduce the risk of harmful exposures and improve the public health of vulnerable populations within these communities.